Cardinal Gianfranco Ravasi said worship of the skeletal figure of a cloaked woman carrying a scythe was a degeneration of religion, the Associated Press reported.
It is a particularly popular symbol in areas of Mexico among drug dealers, as well as those who have suffered extreme violence at the hands of cartels.
Cardinal Ravasi was speaking at a series of events for believers and non-believers on Wednesday, known as the Courtyard of Gentiles, a project started by Pope Benedict XVI in 2009.
He said, the BBC reports: “Religion celebrates life, but here you have death.
“It’s not religion just because it’s dressed up like religion; it’s blasphemous against religion.”
Worship of Santa Meurte is said to soothe a variety of ills, including fending off wrongdoing, carrying out vengeance and stopping lovers from cheating.
And her following is growing in North America too.
Andrew Chesnut, author of "Devoted to Death: Santa Muerte, the Skeleton Saint", says: "Her growth in the United States has been extraordinary.
"Because you can ask her for anything, she has mass appeal and is now gaining a diverse group of followers throughout the country. She's the ultimate multi-tasker."
Blogging for the Huffington Post, he added: “Many Americans perceive her as a malicious figure at best and satanic at worst.
“In 2005 the Mexican government reacted to similar events by revoking the legal rights of a church devoted to her veneration in Mexico City. Let's hope that as the cult of the controversial skeleton saint continues to grow on this side of the border, we uphold our own cherished tradition of religious freedom.”